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Structural and mechanistic mapping of a unique fumarate reductase

Nature Structural Biology volume 6, pages 1108–1112 (1999)Cite this article

Abstract

The 1.8 Å resolution crystal structure of the tetraheme flavocytochrome c3, Fcc3, provides the first mechanistic insight into respiratory fumarate reductases or succinate dehydrogenases. The multi-redox center, three-domain protein shows a 40 Å long 'molecular wire' allowing rapid conduction of electrons through a new type of cytochrome domain onto the active site flavin, driving the reduction of fumarate to succinate. In this structure a malate-like molecule is trapped in the enzyme active site. The interactions between this molecule and the enzyme suggest a clear mechanism for fumarate reduction in which the substrate is polarized and twisted, facilitating hydride transfer from the reduced flavin and subsequent proton transfer. The enzyme active site in the oxidized form is completely buried at the interface between the flavin-binding and the clamp domains. Movement of the cytochrome and clamp domains is postulated to allow release of the product.

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Figure 1: 2Fo - Fc difference electron density.
Figure 2: Structural features of Fcc3.
Figure 3: The active site of Fcc3.
Figure 4: Reaction mechanisms at the Fcc3 active site.

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Acknowledgements

We thank A. Mattevi for the l-aspartate oxidase coordinates, R. Baxter, S. Flitsch, D. Gerloff and S. Webster for helpful discussion and D. Alexeev and A. Gonzalez for help in X-ray data collection. We thank the BBSRC and EMBL for access to synchrotron radiation sources at Daresbury and Hamburg. This work was funded by the UK Biotechnology and Biological Sciences Research Council.

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Authors and Affiliations

  1. Institute of Cell and Molecular Biology, University of Edinburgh, Mayfield Road, Edinburgh, EH9 3JR, UK

    Paul Taylor, Sara L. Pealing, Graeme A. Reid & Malcolm D. Walkinshaw

  2. Department of Chemistry, University of Edinburgh, West Mains Road, Edinburgh, EH9 3JJ, UK

    Sara L. Pealing & Stephen K. Chapman

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  1. Paul Taylor
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Correspondence to Malcolm D. Walkinshaw.

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Taylor, P., Pealing, S., Reid, G. et al. Structural and mechanistic mapping of a unique fumarate reductase. Nat Struct Mol Biol 6, 1108–1112 (1999). https://doi.org/10.1038/70045

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